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Abstract

OBJECTIVE: To compare pregnancy outcomes in women with one prior low-transverse cesarean delivery after induction of labor with pregnancy outcomes after spontaneous labor.

METHODS: This study is an analysis of women with one prior low-transverse cesarean and a singleton gestation who underwent a trial of labor and who were enrolled in a 4-year prospective observational study. Pregnancy outcomes were evaluated according to whether a woman underwent spontaneous labor or labor induction.

RESULTS: Among the 11,778 women studied, vaginal delivery was less likely after induction of labor both in women without and with a prior vaginal delivery (51% versus 65%, P<.001; and 83% versus 88%, P<.001). An increased risk of uterine rupture after labor induction was found only in women with no prior vaginal delivery (1.5% versus 0.8%, P=.02; and 0.6% versus 0.4%, P=.42). Blood transfusion, venous thromboembolism, and hysterectomy were also more common with induction among women without a prior vaginal delivery. No measure of perinatal morbidity was associated with labor induction. An unfavorable cervix at labor induction was not associated with any adverse outcomes except an increased risk of cesarean delivery.

CONCLUSION: Induction of labor in the study population is associated with an increased risk of cesarean delivery in all women with an unfavorable cervix, a statistically significant, albeit clinically small, increase in maternal morbidity in women with no prior vaginal delivery, and no appreciable increase in perinatal morbidity.

LEVEL OF EVIDENCE: II

After peaking in 1996, the vaginal birth after cesarean delivery (VBAC) rate has steadily declined to 13% in 2004.1 This decline has been accompanied by a number of articles that have questioned whether a trial of labor is equally suitable for all women with a prior low-transverse cesarean delivery. Correspondingly, investigators have tried to identify factors predictive of a lower chance of a successful trail of labor as well as a greater chance of uterine rupture, and thereby identify the specific women for whom a trial of labor is less safe and appropriate. 2–5

In contrast to the declining rate of VBAC, the rate of labor induction has been steadily increasing, more than doubling over the last decade to a frequency of more than 20%.6 Thus, the effect of induced versus spontaneous labor in women attempting VBAC is of particular interest. Initial reports suggested that women who underwent labor induction were no more likely than their spontaneously laboring counterparts to have a cesarean delivery or a uterine rupture.7–10 More recent studies, however, have challenged both conclusions, showing a higher rate of both cesarean delivery and uterine rupture among women undergoing labor induction with a prior cesarean delivery.11–14

These inconsistent findings may reflect the methodological differences among prior studies. The results of several studies were not stratified by history of vaginal delivery, a factor that has been shown to be relevant both to trial of labor success and uterine rupture.7–12 Studies of women whose only prior birth was a cesarean delivery did not include outcomes stratified by cervical ripeness, an important predictor of trial of labor success.13,14 Thus, the effect of obstetric history and cervical ripeness on VBAC success and uterine rupture remains unclear. In the present study, we have used prospectively collected and validated data to examine the effect of labor induction on VBAC success and maternal and perinatal health outcomes, controlling for both history of vaginal delivery and cervical status at initiation of induction.

MATERIALS AND METHODS

From 1999 to 2002, a prospective observational study of pregnant women with a prior cesarean delivery was performed at 19 academic medical centers belonging to the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network.4 At each center, trained and certified research nurses utilized hospital records, logbooks, and databases to identify women who were admitted for delivery and who had a history of cesarean delivery. Study subjects’ charts were abstracted for demographic data, medical and obstetric history, and intrapartum and postpartum events. Neonatal charts were additionally abstracted for data relating to the neonatal hospital course until discharge or 120 days after delivery, whichever came first. All data were transmitted weekly to the data coordinating center and were edited for missing, out-of-range, and inconsistent values. Reports of uterine rupture, hypoxic-ischemic encephalopathy, stillbirths, and maternal death underwent secondary review at each clinical center as well as centrally to ensure accuracy of diagnosis.

This analysis concerns those women in the registry with a singleton gestation and one prior low-transverse cesarean delivery who underwent a trial of labor at term (greater than 36 weeks 6 days of gestation). Women with an antepartum intrauterine fetal demise were excluded from analysis. Maternal demographic data, as well as maternal and neonatal health outcomes, were stratified by obstetric history (no prior and prior vaginal delivery) and type of labor (induced and spontaneous). Women were considered to have undergone induction if regular contractions were not present before admission and were initiated either with a uterotonic drug, such as oxytocin, or by the artificial rupture of membranes. Indication for induction was dichotomized into those performed for medical reasons and those performed electively. A medical reason was considered present in the setting of a postterm gestational age (greater than 40 weeks 6 days of gestation), premature rupture of membranes, suspected intrauterine growth restriction, oligohydramnios, nonreassuring fetal testing, or a maternal medical or obstetric condition (eg, cardiac disease, diabetes, and preeclampsia). Postpartum endometritis was defined as a clinical diagnosis of puerperal infection with a temperature at least 37.8°C and without evidence of a nonuterine source of infection. Uterine rupture was defined as a disruption or tear of the uterine muscle and visceral peritoneum or as a separation of the uterine muscle with extension into the bladder or broad ligament and did not include asymptomatic uterine scar dehiscences, which were coded separately.

Those outcomes that were found to be significantly different between women who spontaneously labored and those who underwent induction were further analyzed after stratification by cervical ripeness. Cervical ripeness was ascertained using the modified Bishop score, which correlates more closely with delivery outcome than the original Bishop score.15 In this analysis, a favorable cervix (cervical ripeness) was defined as one with a modified Bishop score of at least 6.16

Last, after univariable analysis identified the outcomes that were significantly associated with induction of labor, multivariable analysis was used to control for differences between women who were induced and those who underwent spontaneous labor and to determine the independent association between these outcomes and labor induction. In cases in which cervical status was also associated with the frequency of a given outcome, the independent contribution of induction with and without a favorable cervix was assessed in the multivariable regression.

Continuous variables were compared by using the Wilcoxon rank-sum test while categorical variables were compared by using either the Fisher exact test or χ2 analysis, as appropriate. Multivariable analysis was performed by using logistic regression. Nominal two-sided P values are reported with statistical significance defined as a P<.05. No adjustment was made for multiple comparisons. SAS 8.2 (SAS Institute, Cary, NC) was used for analysis. Approval for the study was obtained at the Institutional Review Board of each institution.

RESULTS

During the study period, 11,778 women with one prior low-transverse cesarean delivery and a viable singleton gestation presented at term for a trial of labor. A graphical representation of the study population stratified by obstetric history and type of labor is presented in Fig. 1. In this population, 6,132 women (52.1%) had no prior vaginal delivery (primiparous), and 5,646 (47.9%) had a prior vaginal delivery. The frequency of labor induction was similar in these two groups of women (27.7% versus 27.6%, respectively; P=.86). Patient demographic characteristics, stratified by type of labor and history of vaginal delivery, are presented in Table 1. Regardless of their history of vaginal delivery, women who underwent labor induction were more likely to be older, white, and married, to have a higher body mass index, and to deliver a slightly larger infant.

Maternal outcomes, stratified by both history of vaginal delivery and type of labor, are presented in Table 2. There was no maternal mortality in the entire cohort. Regardless of history of vaginal delivery, women who underwent induction of labor were significantly less likely to have a vaginal delivery. Aside from the outcome of vaginal delivery, however, statistically significant differences in maternal outcomes between those women who underwent induction and those who labored spontaneously were limited to the primiparous cohort. Specifically, primiparous women who underwent induction were more likely to experience a uterine rupture, transfusion, venous thromboembolism, and hysterectomy.

Perinatal outcomes stratified by history of vaginal delivery and type of labor are presented in Table 3. Regardless of the history of vaginal delivery, no measure of perinatal morbidity significantly differed between women who were and were not induced.

Data regarding the cervical examination at initiation of labor induction were available for 1,494 primiparous women (87.8%) and 1,374 women (88.2%) with a prior vaginal delivery. After further stratification by cervical ripeness, the maternal outcome variables that were significantly different between women who spontaneously labored and those who underwent induction are summarized in Table 4. Vaginal delivery was significantly more likely when induction was initiated with a favorable cervix than with an unfavorable cervix regardless of whether women had a prior vaginal delivery. The frequency of uterine rupture for primiparous women, however, was similar regardless of cervical status at initiation of labor. The frequency of other maternal morbidities did not differ on the basis of initial cervical status at labor induction.

DISCUSSION

The appropriateness of a labor induction for women attempting a VBAC remains controversial. The continuing controversy exists, to a large degree, because of the conflicting results from studies that have examined the health outcomes of induction of labor in women with a prior cesarean delivery.7–14 Several methodologic reasons may account for these inconsistent results. Many study groups have included women with different numbers of prior cesarean deliveries, different types of cesarean incisions, and different histories with regard to vaginal delivery. 7–12 Thus, the independent effect of an induction of labor in a specific circumstance, such as in a woman whose only prior birth was through a low-transverse cesarean incision, was not possible to discern from these studies. While other investigators have analyzed more specific study populations, retrospective data collection has been a cause for concern. For example, Lydon-Rochelle and colleagues,14 who assessed the chance of uterine rupture after labor induction in women with one prior cesarean delivery, based the diagnosis of uterine rupture on International Classification of Diseases, 9th revision, coding alone, a method with known potential for ascertainment bias.17 Additionally, retrospective analyses have not been able to account for other potentially influential factors, such as cervical status at initiation of induction, and frequently have studied intermediate endpoints.3,13,14

In the present analysis, we restricted the study population to women with a singleton gestation at term and one prior low-transverse cesarean delivery. We chose this group because it represents the majority of women undergoing a trial of labor and limits potentially confounding effects of other factors. In an effort to further ensure that the association of labor induction with trial of labor outcomes was not affected by other potentially confounding factors, the analysis was stratified by history of vaginal delivery and cervical ripeness at the initiation of labor induction. The possibility of ascertainment bias was minimized by the prospective study design, the use of trained abstractors for all data collection, and the reconfirmation of certain health outcomes, such as uterine rupture, by confirmatory chart reviews. Finally, in addition to assessing outcomes such as successful VBAC and uterine rupture, we have examined a more extended set of maternal and neonatal morbidity.

The results of the study indicate that a broad conclusion regarding the appropriateness of labor induction for women with one prior cesarean delivery is unlikely to be a useful approach. Instead, counseling with regard to labor induction will need to take into account certain characteristics, such as whether a woman has had a prior vaginal delivery. Although the overall chance of successful VBAC is greater in women with a prior vaginal birth, these women as well as those without a prior vaginal birth have a decreased chance of a successful VBAC after induction of labor is initiated with an unfavorable cervix.18 In contrast, as demonstrated in the multivariable analysis, an induction of labor with a favorable cervix has a similar rate of successful VBAC in comparison to spontaneous labor in women with one prior cesarean, regardless of prior vaginal delivery.

Whereas labor induction, compared with spontaneous labor, increases the risk of uterine rupture in primiparous women, no significant association between labor induction and uterine rupture was found in women with a prior vaginal delivery. This difference in the association of labor induction with uterine rupture as a function of history of vaginal delivery has not been well documented previously. Few studies have specifically examined the outcome of uterine rupture after induced labors in women with both a prior cesarean delivery and a prior vaginal delivery.19–21 Investigators who have examined this specific subgroup have each analyzed fewer than 100 women with a prior vaginal delivery, thus limiting any conclusions that could be drawn. In the present study, which contains more than 1,500 women with a prior vaginal delivery and an induced labor, there is much greater power to have found a difference. It should be noted that even with this number of women analyzed, the possibility remains that there could be a small absolute increase in uterine rupture with labor induction that would not have been discerned.

With regard to the primiparous women, there has previously been controversy as to the circumstances that predispose a woman to an increased risk of rupture during labor induction. Some investigators have found this increased risk with oxytocin, some have found it with prostaglandin only, and others have determined that an increased risk exists only when prostaglandin and oxytocin are used in combination. 4,12–14,22 The disparity of these results may be due to several disparities in the underlying methodology of these studies. The study by Lydon-Rochelle et al14 that implicated prostaglandin, for example, did not have information as to whether the prostaglandin was used alone or in combination with other agents. In contrast, after analyzing the data by specific circumstance of prostaglandin use and including only women who received intravaginal prostaglandin, Macones et al22 did not find a strong association between prostaglandin agents and uterine rupture, with a small increased risk only when prostaglandin was used sequentially with oxytocin. Neither study accounted for cervical status at initiation of induction, raising the possibility that induction with an unfavorable cervix, which would predispose to use of ripening agents such as prostaglandin, could be the factor underlying any increased risk attributed to prostaglandin.

Our results call into question the supposition that the status of the cervix, rather than the induction agent itself, may be the actual factor associated with an increased risk of uterine rupture, as there was no evidence that rupture or other maternal morbidity was increased in women with an unfavorable cervix at initiation of induction. Also, there was no evidence that prostaglandin agents, either alone or in combination with oxytocin, were associated with a significantly elevated risk of uterine rupture greater than induction undertaken with oxytocin alone. However, given the relatively few patients who received prostaglandin agents, there is limited power in this study to assess this association.

One issue that has been raised with regard to prior studies that have evaluated labor induction after prior cesarean delivery is that the health outcomes usually examined, namely successful VBAC and uterine rupture, are intermediate outcomes, and that the actual association of labor induction with other maternal and perinatal morbidity remains uncertain.3 The present study, which did examine an extended number of these morbidities, allows several conclusions to be drawn. As with uterine rupture, several measures of maternal morbidity are statistically increased in association with labor induction, although only in primiparous women. The frequency of these outcomes does not appear to be highly dependent on whether induction occurs with a favorable or unfavorable cervix. Also, although several measures of maternal morbidity were statistically increased, the attributable risk was small, as no increase greater than 0.9% was seen in either the rates of transfusion, venous thromboembolism, or hysterectomy. Given that this was an observational study, the chance remains that the outcome differences were not due to the labor induction itself, but to other differences in women who undergo labor induction. In an effort to limit this possibility, we performed multivariable regression to adjust for possible confounding variables.

Labor induction was not associated with a statistically significant increase for any measure of perinatal morbidity. For some outcomes, this finding should be reassuring for women who desire a VBAC, but are confronted with the need to iatrogenically initiate labor. For example, this study has 80% power to detect an increase as small as 2.5% in the frequency of special care nursery admission among primiparous women. Even with the present sample size, however, the infrequency of some outcomes, such as hypoxic-ischemic encephalopathy, allows the possibility that an increase in these outcomes could not be discerned in this study.

In this analysis, all women who underwent spontaneous labor, regardless of whether they ultimately received oxytocin augmentation, were compared with those who underwent labor induction. The decision not to stratify separately by augmentation status was made for several reasons. First, augmentation is in and of itself evidence that a labor is not progressing at the same pace as a spontaneous labor. Consequently, finding an increased cesarean delivery rate or maternal complication such as need for transfusion may not be independently associated with the augmentation itself, but the prolonged labor that engendered the augmentation in the first place. Also, this comparison is the relevant comparison from the perspectives of a patient and physician who are discussing whether or not to proceed with labor induction.

Indeed, given the data in this analysis, women who desire a VBAC and are confronted with the decision to undergo labor induction can be counseled that their risk for most serious adverse outcomes is not significantly increased, the adverse outcomes that are increased have a small attributable risk associated with induction, and that even this small attributable risk appears limited to women without a prior vaginal birth. Regardless of history of vaginal delivery, however, women should be aware that induction initiated with an unfavorable cervix may decrease the chance of successful VBAC, and physicians should consider limiting this practice to cases where expectant management is no longer the most reasonable option.

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